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1.
Chemosphere ; 353: 141555, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417497

RESUMEN

Dermal exposure to phosphorus flame retardants (PFRs) has received much attention as a major alternative exposure route in recent years. However, the information regarding dermal exposure via direct contact with a product is limited. In addition, in the commonly used dermal permeability test, the target substance is dissolved in a solvent, which is unrealistic. In this study, a dermal permeability test of PFRs in three car seats was performed using artificial skin. The PFR concentrations in the car seats are 0.12 wt% tris(2-chloroethyl) phosphate (TCEP), 0.030-0.25 wt% tris(2-chloroisopropyl) phosphate (TCPP), 0.15 wt% triphenyl phosphate (TPhP), 0.89 wt% cresyl diphenyl phosphate (CsDPhP), 0.074 wt% tricresyl phosphate (TCsP), and 0.46-4.7 wt% diethylene glycol bis [di (2-chloroisopropyl) phosphate (DEG-BDCIPP). The mean skin permeation rates for a contact time of 24 h are 14 (TCEP), 5.4-160 (TCPP), 0.67 (CsDPhP), 0.38 (TPhP), and 3.3-58 ng cm-2 h-1 (DEG-BDCIPP). The concentrations of TCsP in receptor liquid were lower than the limit of quantification at the contact time of 24 h. The skin permeation rates were significantly affected by the type of car seat (e.g., fabric or non-fabric). The potential dermal TCPP exposure rate for an adult via direct contact with the car seat during the average daily contact time (1.3 h), which was the highest value assessed in this study, was estimated to be 16,000 ng kg-1 day-1, which is higher than that related to inhalation and dust ingestion reported as significant exposure route of PFRs in previous studies. These facts reveal that dermal exposure associated with direct contact with the product might be an important exposure pathway for PFRs.


Asunto(s)
Sistemas de Retención Infantil , Retardadores de Llama , Fosfinas , Piel Artificial , Tritolilfosfatos , Humanos , Adulto , Fósforo , Retardadores de Llama/análisis , Organofosfatos/análisis , Fosfatos , Polvo , Exposición a Riesgos Ambientales
2.
BMC Pharmacol Toxicol ; 24(1): 59, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37924139

RESUMEN

BACKGROUND: Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as adjuvant therapy depending on to its antioxidant properties. We hypothesized that IV N-acetylcysteine is effective in reducing mortality rate compared to supportive treatment alone. METHODS: We searched in PubMed, Scopus, Web of Science, and Cochrane Library databases. We only included randomized controlled trials that assessed the efficacy of IV N-acetylcysteine and supportive treatment versus supportive treatment alone in acute aluminum phosphide poisoning. Four investigators independently screened the studies' results and designed the data extraction sheet. The primary and secondary outcomes were mortality and the need for mechanical ventilation rates. Random effects estimators with weights were used to result in the pooled risk ratios. RESULTS: We included four randomized controlled trials with 177 patients. 91 patients were distributed in N-acetylcysteine group and 86 patients in the control group. Mortality rates in N-acetylcysteine group and in the control group were 43.95% 66.27% respectively. There was a statistically significant reduction in mortality rate after leave out test (pooled risk ratio, 0.5; 95% confidence interval, 0.32-0.77). Regarding the need for mechanical ventilation, it was measured only in three RCTs. It was assessed in 67 patients in N-acetylcysteine group and 60 patients in the control group. 24 patients were ventilated in N-acetylcysteine group (35.8%) and 29 patients in the control group (48.3%). But it was statistically nonsignificant (pooled risk ratio, 0.71; 95% confidence interval, 0.48-1.04). CONCLUSION: Our meta-analysis revealed that IV N-acetylcysteine may be effective in reducing mortality of severe aluminum phosphide poisoning cases. TRIAL REGISTRATION: Registration number in Prospero CRD42022375344 on 25 NOVEMBER 2022, retrospectively registered.


Asunto(s)
Acetilcisteína , Fosfinas , Humanos , Acetilcisteína/uso terapéutico , Antioxidantes , Compuestos de Aluminio
3.
Environ Sci Pollut Res Int ; 30(31): 76595-76605, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37243771

RESUMEN

The process of phosphine production by phosphate-reducing bacteria Pseudescherichia sp. SFM4 has been well studied. Phosphine originates from the biochemical stage of functional bacteria that synthesize pyruvate. Stirring the aggregated bacterial mass and supplying pure hydrogen could lead to an increase of 40 and 44% phosphine production, respectively. Phosphine was produced when bacterial cells agglomerated in the reactor. Extracellular polymeric substances secreted on microbial aggregates promoted the formation of phosphine due to the presence of groups containing phosphorus element. Phosphorus metabolism gene and phosphorus source analysis implied that functional bacteria used anabolic organic phosphorus, especially containing carbon-phosphorus bonds, as a source with [H] as electron donor to produce phosphine.


Asunto(s)
Fosfinas , Fósforo , Fósforo/análisis , Bacterias/metabolismo , Enterobacteriaceae
4.
Food Chem Toxicol ; 169: 113440, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36162615

RESUMEN

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.


Asunto(s)
Retardadores de Llama , Enfermedades Metabólicas , Probióticos , Animales , Retardadores de Llama/toxicidad , Lípidos , Ratones , Obesidad , Organofosfatos , PPAR alfa , PPAR gamma , Fosfatos , Fosfinas , Probióticos/farmacología , Transducción de Señal
5.
J Inorg Biochem ; 236: 111972, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36087434

RESUMEN

Excessive organophosphate flame retardant (OPFR) use in consumer products has been reported to increase human disease susceptibility. However, the adverse effects of tris(2-chloroethyl) phosphate (TCEP) (a chlorinated alkyl OPFR) on the heart remain unknown. In this study, we tested whether cardiac fibrosis occurred in animal models of TCEP (10 mg/kg b.w./day) administered continuously by gavage for 30 days and evaluated the specific role of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). First, we confirmed that TCEP could trigger cardiac fibrosis by histopathological observation and cardiac fibrosis markers. We further verified that cardiac fibrosis occurred in animal models of TCEP exposure accompanied by SERCA2a, SERCA2b and SERCA2c downregulation. Notably, inductively coupled plasma-mass spectrometry (ICP-MS) analysis revealed that the cardiac concentrations of Ca2+ increased by 45.3% after TCEP exposure. Using 4-Isopropoxy-N-(2-methylquinolin-8-yl)benzamide (CDN1163, a small molecule SERCA activator), we observed that Ca2+ overload and subsequent cardiac fibrosis caused by TCEP were both alleviated. Simultaneously, the protein levels of endoplasmic reticulum (ER) markers (protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring protein 1α (IRE1α), eukaryotic initiation factor 2 α (eIF2α)) were upregulated by TCEP, which could be abrogated by CDN1163 pretreatment. Furthermore, we observed that CDN1163 supplementation prevented overactive autophagy induced by TCEP in the heart. Mechanistically, TCEP could lead to Ca2+ overload by inhibiting the expression of SERCA, thereby triggering ER stress and overactive autophagy, eventually resulting in cardiac fibrosis. Together, our results suggest that the Ca2+ overload/ER stress/autophagy axis can act as a driver of cardiotoxicity induced by TCEP.


Asunto(s)
Endorribonucleasas , Retardadores de Llama , Aminoquinolinas , Animales , Autofagia , Benzamidas/metabolismo , Calcio/metabolismo , Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Endorribonucleasas/metabolismo , Endorribonucleasas/farmacología , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2 Eucariótico de Iniciación/farmacología , Fibrosis , Retardadores de Llama/metabolismo , Retardadores de Llama/farmacología , Humanos , Inositol/metabolismo , Inositol/farmacología , Organofosfatos , Fosfatos/metabolismo , Fosfinas , Proteínas Serina-Treonina Quinasas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/farmacología
6.
Angew Chem Int Ed Engl ; 61(40): e202209293, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-35912895

RESUMEN

Herein, cobaloxime is used for the first time as a catalyst for the synthesis of phosphorylated heteroaromatics, which is an intriguing and versatile functional motif. With visible-light irradiation, cobaloxime not only oxidizes phosphine oxides to form phosphorus radicals (P-radicals) for a subsequent reaction with radical acceptor isocyanides or heteroaromatics, but also combines the radical intermediate with ß-H elimination, thereby producing phosphorylated heteroaromatics with only H2 or CH4 as byproduct. Phosphine oxides with dialkyl, alkylaryl, and diaryl substituents could be directly transformed into phosphorylated phenanthridines, benzothiazoles, isoquinolines, and common heteroaromatics. This catalytic system features extremely mild conditions, broad substrate scope and good to excellent yields. Scale-up reaction and sunlight reaction show the great application potential in the green synthesis of important organophosphorus chemicals.


Asunto(s)
Cianuros , Óxidos , Benzotiazoles , Isoquinolinas , Compuestos Organometálicos , Fenantridinas , Fosfinas , Fósforo
7.
Chemistry ; 28(51): e202202074, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-35789048

RESUMEN

The fine-tuning of metal-phosphine-catalyzed reactions relies largely on accessing ever more precisely tuned phosphine ligands by de-novo synthesis. Late-stage C-H functionalization and diversification of commercial phosphines offers rapid access to entire libraries of derivatives based on privileged scaffolds. But existing routes, relying on phosphorus-directed transformations, only yield functionalization of C sp 2 -H bonds in a specific position relative to phosphorus. In contrast to phosphorus-directed strategies, herein we disclose an orthogonal functionalization strategy capable of introducing a range of substituents into previously inaccessible positions on arylphosphines. The strongly coordinating phosphine group acts solely as a bystander in the sterically controlled borylation of bulky phosphines, and the resulting borylated phosphines serve as the supporting ligands for palladium during diversification through phosphine self-assisted Suzuki-Miyaura reactions.


Asunto(s)
Fosfinas , Catálisis , Ligandos , Paladio/química , Fosfinas/química , Fósforo/química
8.
Org Biomol Chem ; 20(31): 6183-6187, 2022 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-35648392

RESUMEN

Advancements in main-group catalysis are contingent on our ability to quantify effects that enhance reactivity in these systems. Herein we report the rates of alkylation for several substituted phosphines. We report that by incorporating a single pinacol boronic ester group in the ortho-position on triphenylphosphine, the rate of substitution with benzyl bromide is approximately 4.7 times faster than the parent compound as measured by initial rates. The corresponding meta- and para-isomers are only 1.3 and 1.5 times as fast, respectively. Using X-ray crystallographic data and quantum chemical calculations, we propose this rate acceleration occurs from an O to P electrostatic interaction that stabilizes the transition state.


Asunto(s)
Boro , Fosfinas , Alquilación , Estructura Molecular , Fosfinas/química , Fósforo
9.
Molecules ; 27(11)2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35684403

RESUMEN

α-Aminophosphonates, -phosphinates, and -phosphine oxides are a group of organophosphorus compounds that were investigated as extraction agents for rare earth (RE) metals and actinoids for the first time in the 1960s. However, more systematic investigations of their extraction properties towards REs and actinoids were not started until the 2010s. Indeed, recent studies have shown that these α-amino-functionalized compounds can outperform the commercial organophosphorus extraction agents in RE separations. They have also proven to be very efficient extraction and precipitation agents for recovering Th and U from RE concentrates. These actinoids coexist with REs in some of the commercially important RE-containing minerals. The efficient separation and purification of REs is becoming more and more important every year as these elements have a pivotal role in many existing technologies. If one also considers the facile synthesis of α-amino-functionalized organophosphorus extractants and precipitation agents, it is expected that they will be increasingly utilized in the extraction chemistry of REs and actinoids in the future. This review collates α-aminophosphonates, -phosphinates, and -phosphine oxides that have been utilized in the separation chemistry of REs and actinoids, including their most relevant synthetic routes and molecular properties. Their extraction and precipitation properties towards REs and actinoids are also discussed.


Asunto(s)
Elementos de Series Actinoides , Metales de Tierras Raras , Organofosfonatos , Uranio , Elementos de Series Actinoides/análisis , Organofosfonatos/química , Óxidos/química , Fosfinas , Torio , Uranio/química
10.
J Med Case Rep ; 16(1): 192, 2022 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-35578361

RESUMEN

BACKGROUND: Aluminum phosphide (rice tablet) is a highly efficient agent for preserving grains against rodents and insects. It accounts for a large number of poisoning cases. Aluminum phosphide poisoning has a high mortality rate of about 90%, and to date, no antidote is available. It releases phosphine gas after exposure to moisture, and this reaction is catalyzed by the acidity of the stomach. Phosphine is then absorbed throughout the respiratory or gastrointestinal tracts and causes toxicity through inhibition of cytochrome c oxidase and formation of highly reactive free radicals. Treatment of patients with aluminum phosphide poisoning is supportive, including mechanical ventilation and vasopressors. The usage of infusion of glucose-insulin-potassium in rice tablet poisoning has been suggested, after its positive beneficial cardiac inotropic effects in patients with beta-blocker and calcium channel blocker poisoning. CASE PRESENTATION: We report the case of a 30-year-old Iranian woman with critical aluminum phosphide poisoning, presented with hypotension and other signs of shock and severe metabolic acidosis, successfully treated with high-dose regular insulin and hypertonic dextrose and discharged from hospital in good condition. In contrast to our previous experiences, in which nearly all patients with critical aluminum phosphide poisoning died, this patient was saved with glucose-insulin-potassium. CONCLUSION: Aluminum phosphide poisoning has a high mortality rate, and to date, no antidote is available. Administration of high-dose intravenous regular insulin and dextrose is suggested as a potential life-saving treatment for patients with critical aluminum phosphide poisoning.


Asunto(s)
Compuestos de Aluminio/química , Hiperinsulinismo , Oryza , Antídotos/uso terapéutico , Glucosa/química , Humanos , Hiperinsulinismo/tratamiento farmacológico , Insulina/uso terapéutico , Irán , Fosfinas/química , Potasio , Comprimidos
11.
Chemosphere ; 294: 133800, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35101429

RESUMEN

Numerous people suffer from accidental or deliberate exposure to different pesticides when poisoning with aluminum phosphate (AlP) is increasing in the eastern countries. Aluminum phosphate is a conventional insecticide that quickly reacts with water or the moistures in the atmosphere and produces fatal phosphine gas, which absorbs quickly by the body. Oral consumption or inhalation of AlP leads to excessive reaction of the body such as fatigue, vomiting, fever, palpitation, vasodilatory shock, increasing blood pressure, cardiac dysfunction, pulmonary congestion, shortness of breath, and death. The garlic smell from the patient's mouth or exhale is one of the methods to recognize the positioning. Due to the lack of individual antidotes, several supportive treatments are required. The present study focused on the available and new therapies that help reduce the effect of AlP poisoning and the mortality rate. The therapies are divided into the antioxidant-related agent and the other agents. The impacts of each agent on the experimental cases are reported.


Asunto(s)
Insecticidas , Intoxicación por Organofosfatos , Plaguicidas , Fosfinas , Intoxicación , Compuestos de Aluminio , Antídotos/uso terapéutico , Humanos , Plaguicidas/toxicidad , Intoxicación/terapia
12.
Dalton Trans ; 51(11): 4423-4428, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35195131

RESUMEN

Metal phosphides have been proved to be potential theranostic agents of tumors. However, the limitations of single-modal imaging or the treatment effect of such materials need to be further improved. Here, we successfully prepared polyvinylpyrrolidone-modified bimetallic nickel cobalt phosphide (NiCoP/PVP) nanoparticles as a theranostic agent of tumors. Owing to the different types of magnetic properties of Ni and Co components, T1- and T2-weighted magnetic resonance imaging (MRI) could be simultaneously achieved to compensate the low accuracy brought about by single-modal MRI. In addition, NiCoP/PVP possesses excellent photothermal properties owing to its obvious absorption in the near-infrared (NIR) region, which endows NiCoP/PVP with high photothermal conversion efficiency (PCE) to serve as a photothermal agent for tumor ablation. Therefore, NiCoP/PVP is a promising theranostic agent for accurate diagnosis and effective treatment of tumors.


Asunto(s)
Antineoplásicos/farmacología , Imagen por Resonancia Magnética , Compuestos Organometálicos/farmacología , Fototerapia , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cobre/química , Cobre/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Rayos Infrarrojos , Ratones , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Níquel/química , Níquel/farmacología , Imagen Óptica , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Tamaño de la Partícula , Fosfinas/química , Fosfinas/farmacología , Povidona/química , Povidona/farmacología , Nanomedicina Teranóstica
13.
Int J Mol Sci ; 23(3)2022 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-35163029

RESUMEN

Levulinic acid and its esters (e.g., ethyl levulinate, EL) are platform chemicals derived from biomass feedstocks that can be converted to a variety of valuable compounds. Reductive amination of levulinates with primary amines and H2 over heterogeneous catalysts is an attractive method for the synthesis of N-alkyl-5-methyl-2-pyrrolidones, which are an environmentally friendly alternative to the common solvent N-methyl-2-pyrrolidone (NMP). In the present work, the catalytic properties of the different nickel phosphide catalysts supported on SiO2 and Al2O3 were studied in a reductive amination of EL with n-hexylamine to N-hexyl-5-methyl-2-pyrrolidone (HMP) in a flow reactor. The influence of the phosphorus precursor, reduction temperature, reactant ratio, and addition of acidic diluters on the catalyst performance was investigated. The Ni2P/SiO2 catalyst prepared using (NH4)2HPO4 and reduced at 600 °C provides the highest HMP yield, which reaches 98%. Although the presence of acid sites and a sufficient hydrogenating ability are important factors determining the pyrrolidone yield, the selectivity also depends on the specific features of EL adsorption on active catalytic sites.


Asunto(s)
Ácidos Levulínicos/química , Níquel/química , Fosfinas/química , Fósforo/farmacología , Dióxido de Silicio/química , Aminación , Catálisis , Hidrogenación , Temperatura
14.
Chemosphere ; 287(Pt 3): 132245, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34543908

RESUMEN

Aluminum phosphide is a well-known hazardous agent used as an agricultural pesticide to protect stored grains from insect damage. However, accidental consumption of a trivial amount of it caused irreversible damage to the human body or even death in acute cases. The present study used taurine and grape seed extract as a natural cardioprotective medicine against aluminum phosphide poisoning by decreasing oxidative stress. The activity of oxidative stress biomarkers (Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase) were evaluated in the cell line model on Human Cardiac Myocyte cells. In the beginning, to clarify the pure impact of aluminum phosphide poison, taurine, and grape seed extract on the human heart cells, their effects on the biomarkers quantity in cell line were measured. Subsequently, the effect of taurine and grape seed extract with various concentrations as a treatment on the oxidative stress biomarkers of the poisoned heart cells were studied. Data analysis reveals that taurine and grape seed extract treatment can successfully diminish the poisoning effect by their antioxidant properties. The oxidative markers values of the poisoned cells were recovered by taurine and grape seed extracts treatment. Taurine (2 g/l) can recover Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase by 56%, 78%, 88%, 78%, when the recovering power of grape seed extract (100 g/l) for the aforementioned enzymes are 56%, 0.71%,74%, 51%, respectively. Therefore, it is clear that the performance of taurine in the recovery of the biomarkers' value is better than grape seed extract.


Asunto(s)
Extracto de Semillas de Uva , Plaguicidas , Vitis , Compuestos de Aluminio , Antioxidantes , Biomarcadores , Extracto de Semillas de Uva/farmacología , Humanos , Estrés Oxidativo , Fosfinas , Taurina/farmacología
15.
Chemistry ; 27(62): 15501-15507, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34524717

RESUMEN

Diastereoselective double C-H heteroarylation of chiral ferrocenes provides valuable compounds with multiple functionalities using mild reaction conditions and simple reagents. Pd-Complexes with chiral mono-protected amino acids afforded corresponding heteroarylated ferrocenyl amines in good yields and high diastereomeric purities. In this way, a variety of indole, thiophene, pyrrole, or furan substituents were introduced to the ferrocene moiety. Furthermore, a range of relevant functional groups, for example ketone, ester, chloro, nitro, or silyl, are tolerated by this method. An alternative combination of amino acid and ferrocenyl amine configurations was leveraged to provide the complementary diastereomeric products. The products of C-H heteroarylation can be transformed into corresponding phosphines. Absolute configurations of CH-activation products were confirmed by the combination of X-ray crystallographic analysis and CD spectroscopy. 19 F NMR kinetic study and DFT calculations provided insights into the reaction mechanism and reasons governing stereoinduction.


Asunto(s)
Paladio , Fosfinas , Aminas , Aminoácidos , Catálisis , Metalocenos
16.
Toxicol Appl Pharmacol ; 427: 115652, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34298059

RESUMEN

Exposure to phosphine (PH3) presents with a host of diverse, non-specific symptoms that span multiple organ systems and is characterized by a high mortality rate. While a comprehensive mechanism for PH3 poisoning remains inconclusive, prior studies have implicated cardiac failure and circulatory compromise as potential pathways central to PH3-induced mortality. In this study, milrinone (MLR), a phosphodiesterase-3 inhibitor used to treat cardiac failure, was investigated as a potential countermeasure for PH3 poisoning. Lethality, physiological responses, and behavioral changes were evaluated in telemetrized female rats pretreated with water (sham) or one of three doses of MLR (40, 200, or 600 µg/kg) and exposed to PH3 (660 ppm for 25-40 min; 16,500-26,400 ppm × min). Animals receiving prophylactic administration of 600 µg/kg of MLR had nominally improved survivability compared to sham animals, although median lethal concentration-time and time of death did not differ substantially between treatment groups. Changes in respiration and behavior induced by PH3 appeared largely unaffected by MLR pretreatment, regardless of dose. Conversely, MLR pretreatment alleviated some aspects of PH3-induced cardiac function impairment, with slight dose-dependent effects observed for cardiac contractility, mean arterial pressure, and QRS duration. Together, these results illustrate the importance of circulatory compromise in PH3 poisoning and highlight the potential viability of MLR as a potential countermeasure option or part of a countermeasure regimen when administered prophylactically at 600 µg/kg.


Asunto(s)
Gasto Cardíaco/efectos de los fármacos , Cardiotónicos/administración & dosificación , Insecticidas/envenenamiento , Milrinona/administración & dosificación , Fosfinas/envenenamiento , Mecánica Respiratoria/efectos de los fármacos , Animales , Gasto Cardíaco/fisiología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Femenino , Exposición por Inhalación/efectos adversos , Dosificación Letal Mediana , Profilaxis Pre-Exposición/métodos , Ratas , Ratas Sprague-Dawley , Mecánica Respiratoria/fisiología , Tasa de Supervivencia/tendencias
17.
Nature ; 594(7862): 217-222, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33910228

RESUMEN

Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile1-4. Drug candidates increasingly contain trifluoromethyl (CF3) and difluoromethyl (CF2H) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life5,6. New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CF2X groups (where X is F or H) in complex drug-like molecules are rare7-13. Pyridines are the most common aromatic heterocycles in pharmaceuticals14, but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development15-17. Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp2-sp3 coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.


Asunto(s)
Carbono/química , Flúor/química , Hidrógeno/química , Fósforo/química , Piridinas/química , Alquilación , Animales , Humanos , Ligandos , Preparaciones Farmacéuticas/química , Farmacocinética , Fosfinas/química
18.
J Pharm Pharmacol ; 73(11): 1539-1546, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33793778

RESUMEN

OBJECTIVES: The effects of Crocin as a cardioprotective material against Aluminum phosphide poisoning by reducing the oxidative stress is investigated. METHODS: The level of biomarkers of oxidative stress (Catalase, Superoxide dismutase, Malondialdehyde and Protein carbonyl) were measured in the cell culture model on Human Cardiac Myocyte cells to detect the protective effect of crocin. Initially, to define the pure impact of aluminum phosphide poison and crocin on the heart cells, their effects on the biomarkers quantity in cell line were measured, separately, using the standard related kits. Later the effect of crocin with different concentration as a treatment on the oxidative stress biomarkers of the poisoned heart cells were monitored. Note that in pre-treatment case, the crocin was initially added to the cells before poisoning them. Data were analyzed using the analysis of variance method. KEY FINDINGS: Results showed that crocin treatment reduced the aluminum phosphide (AlP) poisoning effect significantly. The treatment resulted in substantial deviation in the biomarkers of oxidative stress at the pre- and post-treatment phases for all groups. The oxidative markers values of the poisoned cells were recovered by crocin treatment. CONCLUSIONS: Crocin is proposed as a potentially powerful antioxidant to treat the cardiotoxicity caused by aluminum phosphide poisoning.


Asunto(s)
Compuestos de Aluminio/toxicidad , Antioxidantes/farmacología , Carotenoides/uso terapéutico , Crocus/química , Miocardio/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfinas/toxicidad , Antídotos/farmacología , Antídotos/uso terapéutico , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Biomarcadores/metabolismo , Cardiotoxicidad , Carotenoides/farmacología , Catalasa/metabolismo , Corazón/efectos de los fármacos , Humanos , Malondialdehído/metabolismo , Miocardio/citología , Miocitos Cardíacos/metabolismo , Plaguicidas/toxicidad , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Carbonilación Proteica , Superóxido Dismutasa/metabolismo
19.
Molecules ; 26(2)2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33430439

RESUMEN

Dendrimers are hyperbranched macromolecules, which are synthesized step-by-step by the repetition of a series of reactions. While many different types of dendrimers are known, this review focusses on the use of trivalent phosphorus derivatives (essentially phosphines and phosphoramidites) for the synthesis of dendrimers. The first part presents dendrimers constituted of phosphines at each branching point. The other parts display the use of trivalent phosphorus derivatives during the synthesis of dendrimers. Different types of reactions have been applied to phosphines. The very first examples of phosphorus-containing dendrimers were obtained by the alkylation of phosphines. Then, several families of dendrimers were elaborated by reaction of phosphoramidites. Such a type of reaction is the base of the solid phase synthesis of oligonucleotides; it has been applied in particular for the synthesis of dendrimers constituted of oligonucleotides. Finally, the Staudinger reaction between phosphines and azides afforded different families of dendrimers, and was at the origin of accelerated methods of synthesis of dendrimers. Besides, the reactivity of the P=N-P=S linkages created by this reaction led to very original dendritic structures.


Asunto(s)
Dendrímeros/química , Fósforo/química , Alquilación , Técnicas de Química Sintética , Dendrímeros/síntesis química , Estructura Molecular , Compuestos Organofosforados/química , Fosfinas/química
20.
J Chromatogr A ; 1637: 461833, 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33373796

RESUMEN

The reliable determination of arsine (AsH3) and phosphine (PH3) in hydrogen (H2), nitrogen (N2) and liquefied petroleum gas (LPG) is of great importance because of its drastic effects on the efficiency of catalysts, as well as the strict regulations associated with health, safety and environmental issues. It is challenging for an analyst to determine the parts per billion of AsH3 and PH3 in H2, N2, and LPG at low and high pressures without collection procedures using adsorption, desorption, and dissolution techniques. To overcome this analytical need an analytical methodology was developed, employing a variable pressure sampler (VPS) coupled to a gas chromatograph (GC) with mass spectrometry (MS) for the identification and quantification of traces of AsH3 and PH3. The instrumentation, tubing and accessories of the VPS were made of passivated steel to avoid losses from absorption of AsH3 and PH3 in the steel which would generate significant analytical problems. The VPS had a homogeneous heating block that prevented analyte losses from condensation. With the VPS, 24 AsH3 and PH3 standards were prepared between 0.005 and 0.1 mg kg-1 in balance of H2, N2 and LPG. The separation and quantification of the analytes was achieved with an improved GC with 4 valves and 5 columns in series that guaranteed the elimination of impurities. The proposed method was optimized in VPS and GC-MS and then validated showing highly accaptable linearity (r2 > 0.9999), detection limits (<0.0009 mg kg-1), limits of quantification (<0.003 mg kg-1), intra-day and inter-day precision and accuracy (<1.14% and ≤3.0% respectively), recovery for the standard addition (86-109%), P values> 0.05 for the test Student's t paired who evaluated the effect of the matrix on pressure and concentration. The speed of analysis was high (<5.2 min). The method was applied to real samples, showing values between 0.005 and 0.1 mg kg-1 and an effect on the efficiency of the Ziegler Natta catalyst between 5 and 56%.


Asunto(s)
Arsenicales/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Hidrógeno/química , Nitrógeno/química , Petróleo/análisis , Fosfinas/análisis , Humanos , Límite de Detección , Reproducibilidad de los Resultados
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